The undersigned cancer patient, provider, and research
organizations appreciate the opportunity to provide
advice regarding the development of a strategic plan on
drug shortages. Our comments will focus on
improving the methods and timeliness of notice regarding
shortages, identifying and assessing alternative
manufacturing sites and entities for drugs and
biologicals in shortage situation, evaluating possible
incentives for entities to begin or expand manufacturing
of drugs in short supply, and developing strategies to
assess and address the impact of shortages on clinical
trials.

During the last several years, diverse cancer community
stakeholders have described the significant impact of
cancer drug shortages on cancer care. Physicians
have reported the pressure to find alternative treatment
options when critical cancer drugs are unavailable;
physicians, pharmacists, and nurses have described hours
spent managing shortages and finding substitute drugs;
patients have expressed their fears about receiving a
therapy that is described as less than optimal; and
clinical researchers have reported abandonment of
studies because a drug crucial to the trial was simply
not available.

Pediatric
researchers have recently described the impact of drug
shortages on long-term health outcomes.A December
27, 2012, study in the New England
Journal of Medicine found that the substitution
of cyclophosphamide for mechlorethamine in the
Stanford V regimen for children diagnosed with
high-risk and intermediate-risk Hodgkin’s lymphoma was
significantly less effective.[1]Cyclophosphamide
was substituted only when shortages of mechlorethamine
forced the change.The authors found that 75% of those treated
with cyclophosphamide enjoyed 2-year event-free
survival, compared to 88% with mechlorethamine.The authors
warn, “Our results suggest that even promising
substitute regimens should be examined carefully
before adoption; what might appear to be a suitable
alternative regimen may result in an inferior outcome
– an intolerable situation for young people with
curable diseases.”

Shortages of drugs and biologicals result in intolerable
situations for both children and adults, and we urge
that the development of the strategic plan be approached
with a sense of urgency, creativity, and aggressiveness
to find solutions to the problem of drug shortages.

We will address several of the specific topics
identified by the Food and Drug Administration (FDA) in
its Request for Comments.

1.New ideas to encourage
high-quality manufacturing and to facilitate expansion
of manufacturing capacity.

We
understand that in a number of cases, FDA has been able
to identify drug manufacturers who could respond to drug
shortages by expanding manufacturing capacity for
current products, opening facilities to begin
manufacture of a drug or biological, or resuming
production of a drug or biological in cases where
manufacturing had been interrupted. These
solutions have been achieved primarily through
aggressive and creative management by FDA, combined with
rapid action by responsive manufacturers. We urge
the agency, in developing its strategic plan, to
consider incentives that might provide additional
encouragement for manufacturers to resolve
shortages. These might include waivers of
application fees for new drug applications or
abbreviated new drug applications and additional (and
possibly transferable) exclusivity for products in the
same therapeutic areas as the drug in shortage.
These options may be beyond the current authority of
FDA, but they might be evaluated in a strategic plan to
ascertain whether legislation would be necessary to
provide FDA authority to implement these reforms.
2.Incentives that federal
agencies, separately or in partnership with FDA, might
provide to prevent shortages.

We recommend that FDA evaluate steps that it and other
federal agencies might take to form partnerships not
simply with each other but with potential manufacturers
to address or mitigate shortages. The federal
government has experience in partnering with or funding
industry partners for the manufacture of vaccines.
We urge that, as part of the strategic plan, the past
experience related to vaccine manufacturing be evaluated
and any promising models be considered for replication
to address shortages of drugs and biologicals.

3.Communications to
alleviate potential or actual shortages.

We recommend changes in the methods for communicating
shortages, and we urge that special attention be
directed to 1) communication with patients, and 2)
collaboration with patient organizations to strengthen
outreach to patients who need information about
shortages. In developing the strategic plan on
drug shortages, FDA should consider the following
recommendations.

FDA web pages should be improved so that
patient navigation is facilitated. We
recommended that the web pages be modified so that
patients can search for products in a shortage
situation under categories including indication and
disease type. We also suggest that more
information be provided about the reasons for the
shortage, so that patients and their cancer care
teams can make informed decisions about alternative
treatments. For example, knowledge about the
cause of the shortage will permit the patient to
make a decision to delay or alter treatment in the
short term or to make more complete changes with
regard to treatment.

FDA should consider partnering with the
National Cancer Institute (NCI) or other offices and
institutes at the National Institutes of Health
(NIH) to develop a fact sheet or guidance document
that patients could utilize in discussions with
their care team about alternative treatment options
if they are confronted with drug shortages. This
document might be in the form of a list of questions
that would guide decisions about alternative
treatments.

The agency should consider partnerships
with patient advocacy groups in the communication of
drug shortages to those groups’ constituents.
FDA might evaluate a simple and straightforward
process through which organizations would partner
with FDA to send alerts about shortages to specific
patient populations. Partnering organizations
should be provided updates on numbers of shortages,
shortages by disease category, length of shortages,
and other important variables, to assist them in
communicating with the public about shortages and
decision-making regarding treatment alternatives.

Additional communication strategies
targeting patients and patient organizations should
be evaluated by FDA. These communication
optionsshould include
social media and email communications targeted
according to disease category.

4.Impact of shortages on
clinical trials.

To assist in its decision-making related to management
and mitigation of the impact of drug shortages on
clinical trials, FDA should seek input from a number of
agencies and organizations. We recommend
that FDA seek advice related to drug shortages and
clinical trials from NCI, which has deep knowledge about
clinical trials supported with NCI funds; the FDA Office
of Hematology and Oncology Products; the Coalition of
Cancer Cooperative Groups; cancer centers; and the
American Society of Clinical Oncology and other
professional groups. These organizations and
agencies and others can provide FDA advice about the
impact of drug shortages on clinical trials to date as
well as guidance about how to manage drug supplies going
forward to ensure completion – rather than abandonment –
of clinical trials. We are recommending that these
entities be consulted during the development of the
strategic plan and that a mechanism be created for
obtaining ongoing input regarding clinical trials from
these groups.

We understand that economic solutions, including
possible changes in the reimbursement for drugs that are
in short supply, are beyond the scope of this
study. We believe that changes in third-party
payment may be necessary to address drug shortages in a
comprehensive and conclusive way, and we will encourage
those changes to the appropriate decision-makers.

We appreciate the opportunity to comment on the FDA drug
shortages strategic plan.